Alzheimer's disease occurs in middle and late life and is defined clinically by a dementia syndrome. The natural history and risks/prognostic factors are not clear, and the causes remain unknown. No effective therapy is yet available. Analyses of brain tissue reveal degeneration of specific neuronal populations and the presence of senile plaques and neurofibrillary tangles. Alterations in transmitter-specific markers including those of the basal forebrain cholinergic systems and, in some cases, of the noradrenergic, somatostatingeric, and other system have also been reported. At present, the relationships between clinical abnormalities and the chemical and structural pathology of the brain are not clear. The principal goals of the Alzheimer's Disease Research Center (ADRC) are to provide the staff, environment, shared resources, and ideas for clinical neuropathological and neurochemical investigations of these problems. The ADRC will provide: administrative staff (Core A); patient populations (Core B); biostatistical programs (Cores A, B, and C); neuropathological/neurochemical analyses (Core C); state-of-the-art computer-imaging technology for quantitating changes in numbers of nerve cells and in structural pathologies of specific neuronal components (Core C); and training/information transfer programs (Core D). In addition, the ADRC will support basic research on: the organization of the normal primate brain (Project A and Pilot C); changes in brain structure/function in aging (Project A); development and characterization of animal models resembling AD (Projects A and B and Pilot F); the issue of regeneration and repair processes in the central nervous system (Project B and Pilot A); and the development of new approaches to therapy of AD, including the use of trophic factors, such as nerve growth factor (Pilot D) and intracerebral grafts of neuronal cells (Pilots A and F). The long-term goal of the ADRC is to encourage new investigators and innovative research in this field so that we may eventually understand the abnormal biological processes occurring in Alzheimer-type dementia and, therefore, devise more rational treatments for these unfortunate individuals.